ADVERSE REACTIONS
The following are discussed in more detail in other sections of the labeling:
- Increased mortality in elderly patients with dementia-related psychosis [see
Boxed Warning
and
Warnings and Precautions (5.1) ]
- Cerebrovascular adverse events, including stroke, in elderly patients with dementia-related psychosis [see
Warnings and Precautions (5.2) ]
- Neuroleptic malignant syndrome [see
Warnings and Precautions (5.3) ]
- Tardive dyskinesia [see
Warnings and Precautions (5.4) ]
- Metabolic Changes (Hyperglycemia and diabetes mellitus, Dyslipidemia, and Weight Gain) [see
Warnings and Precautions (5.5) ]
- Hyperprolactinemia [see
Warnings and Precautions (5.6) ]
- Orthostatic hypotension [see
Warnings and Precautions (5.7) ]
- Leukopenia, neutropenia, and agranulocytosis [see Warnings and Precautions ]
- Potential for cognitive and motor impairment [see Warnings and Precautions ]
- Seizures [see
Warnings and Precautions]
- Dysphagia [see
Warnings and Precautions (5.11) ]
- Priapism [see
Warnings and Precautions (5.12) ]
- Disruption of body temperature regulation [see
Warnings and Precautions (5.13) ]
- Patients with Phenylketonuria [see
Warnings and Precautions (5.14) ].
The most common adverse reactions in clinical trials (>5% and twice placebo) were parkinsonism, akathisia, dystonia, tremor, sedation, dizziness, anxiety, blurred vision, nausea, vomiting, upper abdominal pain, stomach discomfort, dyspepsia, diarrhea, salivary hypersecretion, constipation, dry mouth, increased appetite, increased weight, fatigue, rash, nasal congestion, upper respiratory tract infection, nasopharyngitis, and pharyngolaryngeal pain.
The most common adverse reactions that were associated with discontinuation from clinical trials (causing discontinuation in >1% of adults and/or >2% of pediatrics) were nausea, somnolence, sedation, vomiting, dizziness, and akathisia [see
Adverse Reactions, Discontinuations Due to Adverse Reactions (6.1) ].
The data described in this section are derived from a clinical trial database consisting of 9803 adult and pediatric patients exposed to one or more doses of RISPERDAL® for the treatment of schizophrenia, bipolar mania, autistic disorder, and other psychiatric disorders in pediatrics and elderly patients with dementia. Of these 9803 patients, 2687 were patients who received RISPERDAL® while participating in double-blind, placebo-controlled trials. The conditions and duration of treatment with RISPERDAL® varied greatly and included (in overlapping categories) double-blind, fixed- and flexible-dose, placebo- or active-controlled studies and open-label phases of studies, inpatients and outpatients, and short-term (up to 12 weeks) and longer-term (up to 3 years) exposures. Safety was assessed by collecting adverse events and performing physical examinations, vital signs, body weights, laboratory analyses, and ECGs.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Commonly-Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials – Schizophrenia
Adult Patients with Schizophrenia
Table 8 lists the adverse reactions reported in 2% or more of RISPERDAL®-treated adult patients with schizophrenia in three 4- to 8-week, double-blind, placebo-controlled trials.
Table 8. Adverse Reactions in ≥2% of RISPERDAL®-Treated Adult Patients (and greater than placebo) with Schizophrenia in Double-Blind, Placebo-Controlled Trials
|
Percentage of Patients Reporting Reaction |
|
RISPERDAL®
|
|
System/Organ Class Adverse Reaction |
2–8 mg per day (N=366) |
>8–16 mg per day (N=198) |
Placebo (N=225) |
Cardiac Disorders
|
|
|
|
Tachycardia |
1 |
3 |
0 |
Eye Disorders
|
|
|
|
Vision blurred |
3 |
1 |
1 |
Gastrointestinal Disorders
|
|
|
|
Nausea |
9 |
4 |
4 |
Constipation |
8 |
9 |
6 |
Dyspepsia |
8 |
6 |
5 |
Dry mouth |
4 |
0 |
1 |
Abdominal discomfort |
3 |
1 |
1 |
Salivary hypersecretion |
2 |
1 |
<1 |
Diarrhea |
2 |
1 |
1 |
General Disorders
|
|
|
|
Fatigue |
3 |
1 |
0 |
Chest pain |
2 |
2 |
1 |
Asthenia |
2 |
1 |
<1 |
Infections and Infestations
|
|
|
|
Nasopharyngitis |
3 |
4 |
3 |
Upper respiratory tract infection |
2 |
3 |
1 |
Sinusitis |
1 |
2 |
1 |
Urinary tract infection |
1 |
3 |
0 |
Investigations
|
|
|
|
Blood creatine phosphokinase increased |
1 |
2 |
<1 |
Heart rate increased |
<1 |
2 |
0 |
Musculoskeletal and Connective Tissue Disorders
|
|
|
|
Back pain |
4 |
1 |
1 |
Arthralgia |
2 |
3 |
<1 |
Pain in extremity |
2 |
1 |
1 |
Nervous System Disorders
|
|
|
|
Parkinsonism *
|
14 |
17 |
8 |
Akathisia
|
10 |
10 |
3 |
Sedation |
10 |
5 |
2 |
Dizziness |
7 |
4 |
2 |
Dystonia
|
3 |
4 |
2 |
Tremor
|
2 |
3 |
1 |
Dizziness postural |
2 |
0 |
0 |
Psychiatric Disorders
|
|
|
|
Insomnia |
32 |
25 |
27 |
Anxiety |
16 |
11 |
11 |
Respiratory, Thoracic and Mediastinal Disorders
|
|
|
|
Nasal congestion |
4 |
6 |
2 |
Dyspnea |
1 |
2 |
0 |
Epistaxis |
<1 |
2 |
0 |
Skin and Subcutaneous Tissue Disorders
|
|
|
|
Rash |
1 |
4 |
1 |
Dry skin |
1 |
3 |
0 |
Vascular Disorders
|
|
|
|
Orthostatic hypotension |
2 |
1 |
0 |
Pediatric Patients with Schizophrenia
Table 9 lists the adverse reactions reported in 5% or more of RISPERDAL®-treated pediatric patients with schizophrenia in a 6-week double-blind, placebo-controlled trial.
Table 9. Adverse Reactions in ≥5% of RISPERDAL®-Treated Pediatric Patients (and greater than placebo) with Schizophrenia in a Double-Blind Trial
|
Percentage of Patients Reporting Reaction |
|
RISPERDAL®
|
|
System/Organ Class Adverse Reaction |
1–3 mg per day (N=55) |
4–6 mg per day (N=51) |
Placebo (N=54) |
Gastrointestinal Disorders
|
|
|
|
Salivary hypersecretion |
0 |
10 |
2 |
Nervous System Disorders
|
|
|
|
Sedation |
24 |
12 |
4 |
Parkinsonism *
|
16 |
28 |
11 |
Tremor |
11 |
10 |
6 |
Akathisia
|
9 |
10 |
4 |
Dizziness |
7 |
14 |
2 |
Dystonia
|
2 |
6 |
0 |
Psychiatric Disorders
|
|
|
|
Anxiety |
7 |
6 |
0 |
Commonly-Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials – Bipolar Mania
Adult Patients with Bipolar Mania
Table 10 lists the adverse reactions reported in 1% or more of RISPERDAL®-treated adult patients with bipolar mania in four 3-week, double-blind, placebo-controlled monotherapy trials.
Table 10. Adverse Reactions in ≥2% of RISPERDAL®-Treated Adult Patients (and greater than placebo) with Bipolar Mania in Double-Blind, Placebo-Controlled Monotherapy Trials
|
Percentage of Patients Reporting Reaction |
System/Organ Class Adverse Reaction |
RISPERDAL®
1–6 mg per day (N=448) |
Placebo (N=424) |
Eye Disorders
|
|
|
Vision blurred |
2 |
1 |
Gastrointestinal Disorders
|
|
|
Nausea |
5 |
2 |
Diarrhea |
3 |
2 |
Salivary hypersecretion |
3 |
1 |
Stomach discomfort |
2 |
<1 |
General Disorders
|
|
|
Fatigue |
2 |
1 |
Nervous System Disorders
|
|
|
Parkinsonism *
|
25 |
9 |
Sedation |
11 |
4 |
Akathisia
|
9 |
3 |
Tremor
|
6 |
3 |
Dizziness |
6 |
5 |
Dystonia
|
5 |
1 |
Lethargy |
2 |
1 |
Table 11 lists the adverse reactions reported in 2% or more of RISPERDAL®-treated adult patients with bipolar mania in two 3-week, double-blind, placebo-controlled adjuvant therapy trials.
Table 11. Adverse Reactions in ≥2% of RISPERDAL®-Treated Adult Patients (and greater than placebo) with Bipolar Mania in Double-Blind, Placebo-Controlled Adjunctive Therapy Trials
|
Percentage of Patients Reporting Reaction |
System/Organ Class |
RISPERDAL® + Mood Stabilizer |
Placebo + Mood Stabilizer |
Adverse Reaction |
(N=127) |
(N=126) |
Cardiac Disorders
|
|
|
Palpitations |
2 |
0 |
Gastrointestinal Disorders
|
|
|
Dyspepsia |
9 |
8 |
Nausea |
6 |
4 |
Diarrhea |
6 |
4 |
Salivary hypersecretion |
2 |
0 |
General Disorders
|
|
|
Chest pain |
2 |
1 |
Infections and Infestations
|
|
|
Urinary tract infection |
2 |
1 |
Nervous System Disorders
|
|
|
Parkinsonism *
|
14 |
4 |
Sedation |
9 |
4 |
Akathisia
|
8 |
0 |
Dizziness |
7 |
2 |
Tremor |
6 |
2 |
Lethargy |
2 |
1 |
Psychiatric Disorders
|
|
|
Anxiety |
3 |
2 |
Respiratory, Thoracic and Mediastinal Disorders
|
|
|
Pharyngolaryngeal pain |
5 |
2 |
Cough |
2 |
0 |
Pediatric Patients with Bipolar Mania
Table 12 lists the adverse reactions reported in 5% or more of RISPERDAL®-treated pediatric patients with bipolar mania in a 3-week double-blind, placebo-controlled trial.
Table 12. Adverse Reactions in ≥5% of RISPERDAL®-Treated Pediatric Patients (and greater than placebo) with Bipolar Mania in Double-Blind, Placebo-Controlled Trials
|
Percentage of Patients Reporting Reaction |
|
RISPERDAL ®
|
|
System/Organ Class Adverse Reaction |
0.5–2.5 mg per day (N=50) |
3–6 mg per day (N=61) |
Placebo (N=58) |
Eye Disorders
|
|
|
|
Vision blurred |
4 |
7 |
0 |
Gastrointestinal Disorders
|
|
|
|
Abdominal pain upper |
16 |
13 |
5 |
Nausea |
16 |
13 |
7 |
Vomiting |
10 |
10 |
5 |
Diarrhea |
8 |
7 |
2 |
Dyspepsia |
10 |
3 |
2 |
Stomach discomfort |
6 |
0 |
2 |
General Disorders
|
|
|
|
Fatigue |
18 |
30 |
3 |
Metabolism and Nutrition Disorders
|
|
|
|
Increased appetite |
4 |
7 |
2 |
Nervous System Disorders
|
|
|
|
Sedation |
42 |
56 |
19 |
Dizziness |
16 |
13 |
5 |
Parkinsonism *
|
6 |
12 |
3 |
Dystonia
|
6 |
5 |
0 |
Akathisia
|
0 |
8 |
2 |
Psychiatric Disorders
|
|
|
|
Anxiety |
0 |
8 |
3 |
Respiratory, Thoracic and Mediastinal Disorders
|
|
|
|
Pharyngolaryngeal pain |
10 |
3 |
5 |
Skin and Subcutaneous Tissue Disorders
|
|
|
|
Rash |
0 |
7 |
2 |
Commonly-Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials - Autistic Disorder
Table 13 lists the adverse reactions reported in 5% or more of RISPERDAL®-treated pediatric patients treated for irritability associated with autistic disorder in two 8-week, double-blind, placebo-controlled trials and one 6-week double-blind, placebo-controlled study.
Table 13. Adverse Reactions in ≥5% of RISPERDAL®-Treated Pediatric Patients (and greater than placebo) Treated for Irritability Associated with Autistic Disorder in Double-Blind, Placebo-Controlled Trials
|
Percentage of Patients Reporting Reaction |
System/Organ Class |
RISPERDAL®
0.5–4.0 mg/day |
Placebo |
Adverse Reaction |
(N=107) |
(N=115) |
Gastrointestinal Disorders
|
|
|
Vomiting |
20 |
17 |
Constipation |
17 |
6 |
Dry mouth |
10 |
4 |
Nausea |
8 |
5 |
Salivary hypersecretion |
7 |
1 |
General Disorders and Administration Site Conditions |
|
|
Fatigue |
31 |
9 |
Pyrexia |
16 |
13 |
Thirst |
7 |
4 |
Infections and Infestations
|
|
|
Nasopharyngitis |
19 |
9 |
Rhinitis |
9 |
7 |
Upper respiratory tract infection |
8 |
3 |
Investigations
|
|
|
Weight increased |
8 |
2 |
Metabolism and Nutrition Disorders
|
|
|
Increased appetite |
44 |
15 |
Nervous System Disorders
|
|
|
Sedation |
63 |
15 |
Drooling |
12 |
4 |
Headache |
12 |
10 |
Tremor |
8
|
1
|
Dizziness |
8 |
2 |
Parkinsonism *
|
8 |
1 |
Renal and Urinary Disorders
|
|
|
Enuresis |
16 |
10 |
Respiratory, Thoracic and Mediastinal Disorders
|
|
|
Cough |
17 |
12 |
Rhinorrhea |
12 |
10 |
Nasal congestion |
10 |
4 |
Skin and Subcutaneous Tissue Disorders
|
|
|
Rash |
8 |
5 |
Other Adverse Reactions Observed During the Clinical Trial Evaluation of Risperidone
The following additional adverse reactions occurred across all placebo-controlled, active-controlled, and open-label studies of RISPERDAL in adults and pediatric patients.
Blood and Lymphatic System Disorders: anemia, granulocytopenia, neutropenia
Cardiac Disorders: sinus bradycardia, sinus tachycardia, atrioventricular block first degree, bundle branch block left, bundle branch block right, atrioventricular block
Ear and Labyrinth Disorders: ear pain, tinnitus
Endocrine Disorders: hyperprolactinemia
Eye Disorders: ocular hyperemia, eye discharge, conjunctivitis, eye rolling, eyelid edema, eye swelling, eyelid margin crusting, dry eye, lacrimation increased, photophobia, glaucoma, visual acuity reduced
Gastrointestinal Disorders: dysphagia, fecaloma, fecal incontinence, gastritis, lip swelling, cheilitis, aptyalism
General Disorders: edema peripheral, thirst, gait disturbance, influenza-like illness, pitting edema, edema, chills, sluggishness, malaise, chest discomfort, face edema, discomfort, generalized edema, drug withdrawal syndrome, peripheral coldness, feeling abnormal
Immune System Disorders: drug hypersensitivity
Infections and Infestations: pneumonia, influenza, ear infection, viral infection, pharyngitis, tonsillitis, bronchitis, eye infection, localized infection, cystitis, cellulitis, otitis media, onychomycosis, acarodermatitis, bronchopneumonia, respiratory tract infection, tracheobronchitis, otitis media chronic
Investigations: body temperature increased, blood prolactin increased, alanine aminotransferase increased, electrocardiogram abnormal, eosinophil count increased, white blood cell count decreased, blood glucose increased, hemoglobin decreased, hematocrit decreased, body temperature decreased, blood pressure decreased, transaminases increased
Metabolism and Nutrition Disorders: decreased appetite, polydipsia, anorexia
Musculoskeletal and Connective Tissue Disorders: joint stiffness, joint swelling, musculoskeletal chest pain, posture abnormal, myalgia, neck pain, muscular weakness, rhabdomyolysis
Nervous System Disorders: balance disorder, disturbance in attention, dysarthria, unresponsive to stimuli, depressed level of consciousness, movement disorder, transient ischemic attack, coordination abnormal, cerebrovascular accident, speech disorder, syncope, loss of consciousness, hypoesthesia, tardive dyskinesia, dyskinesia, cerebral ischemia, cerebrovascular disorder, neuroleptic malignant syndrome, diabetic coma, head titubation
Psychiatric Disorders: agitation, blunted affect, confusional state, middle insomnia, nervousness, sleep disorder, listlessness, libido decreased, and anorgasmia
Renal and Urinary Disorders: enuresis, dysuria, pollakiuria, urinary incontinence
Reproductive System and Breast Disorders: menstruation irregular, amenorrhea, gynecomastia, galactorrhea, vaginal discharge, menstrual disorder, erectile dysfunction, retrograde ejaculation, ejaculation disorder, sexual dysfunction, breast enlargement
Respiratory, Thoracic, and Mediastinal Disorders: wheezing, pneumonia aspiration, sinus congestion, dysphonia, productive cough, pulmonary congestion, respiratory tract congestion, rales, respiratory disorder, hyperventilation, nasal edema
Skin and Subcutaneous Tissue Disorders: erythema, skin discoloration, skin lesion, pruritus, skin disorder, rash erythematous, rash papular, rash generalized, rash maculopapular, acne, hyperkeratosis, seborrheic dermatitis
Vascular Disorders: hypotension, flushing
Additional Adverse Reactions Reported with RISPERDAL® CONSTA®
The following is a list of additional adverse reactions that have been reported during the premarketing evaluation of RISPERDAL® CONSTA®, regardless of frequency of occurrence:
Cardiac Disorders: bradycardia
Ear and Labyrinth Disorders: vertigo
Eye Disorders: blepharospasm
Gastrointestinal Disorders: toothache, tongue spasm
General Disorders and Administration Site Conditions: pain
Infections and Infestations: lower respiratory tract infection, infection, gastroenteritis, subcutaneous abscess
Injury and Poisoning: fall
Investigations: weight decreased, gamma-glutamyltransferase increased, hepatic enzyme increased
Musculoskeletal, Connective Tissue, and Bone Disorders: buttock pain
Nervous System Disorders: convulsion, paresthesia
Psychiatric Disorders: depression
Skin and Subcutaneous Tissue Disorders: eczema
Vascular Disorders: hypertension
Discontinuations Due to Adverse Reactions
Schizophrenia - Adults
Approximately 7% (39/564) of RISPERDAL®-treated patients in double-blind, placebo-controlled trials discontinued treatment due to an adverse reaction, compared with 4% (10/225) who were receiving placebo. The adverse reactions associated with discontinuation in 2 or more RISPERDAL®-treated patients were:
Table 14. Adverse Reactions Associated With Discontinuation in 2 or More RISPERDAL®-Treated Adult Patients in Schizophrenia Trials
|
RISPERDAL®
|
|
Adverse Reaction |
2–8 mg/day (N=366) |
>8–16 mg/day (N=198) |
Placebo (N=225) |
Dizziness |
1.4% |
1.0% |
0% |
Nausea |
1.4% |
0% |
0% |
Vomiting |
0.8% |
0% |
0% |
Parkinsonism |
0.8% |
0% |
0% |
Somnolence |
0.8% |
0% |
0% |
Dystonia |
0.5% |
0% |
0% |
Agitation |
0.5% |
0% |
0% |
Abdominal pain |
0.5% |
0% |
0% |
Orthostatic hypotension |
0.3% |
0.5% |
0% |
Akathisia |
0.3% |
2.0% |
0% |
Discontinuation for extrapyramidal symptoms (including Parkinsonism, akathisia, dystonia, and tardive dyskinesia) was 1% in placebo-treated patients, and 3.4% in active control-treated patients in a double-blind, placebo- and active-controlled trial.
Schizophrenia - Pediatrics
Approximately 7% (7/106), of RISPERDAL®-treated patients discontinued treatment due to an adverse reaction in a double-blind, placebo-controlled trial, compared with 4% (2/54) placebo-treated patients. The adverse reactions associated with discontinuation for at least one RISPERDAL®-treated patient were dizziness (2%), somnolence (1%), sedation (1%), lethargy (1%), anxiety (1%), balance disorder (1%), hypotension (1%), and palpitation (1%).
Bipolar Mania - Adults
In double-blind, placebo-controlled trials with RISPERDAL® as monotherapy, approximately 6% (25/448) of RISPERDAL®-treated patients discontinued treatment due to an adverse event, compared with approximately 5% (19/424) of placebo-treated patients. The adverse reactions associated with discontinuation in RISPERDAL®-treated patients were:
Table 15. Adverse Reactions Associated With Discontinuation in 2 or More RISPERDAL®-Treated Adult Patients in Bipolar Mania Clinical Trials
Adverse Reaction |
RISPERDAL®
1–6 mg/day (N=448) |
Placebo (N=424) |
Parkinsonism |
0.4% |
0% |
Lethargy |
0.2% |
0% |
Dizziness |
0.2% |
0% |
Alanine aminotransferase increased |
0.2% |
0.2% |
Aspartate aminotransferase increased |
0.2% |
0.2% |
Bipolar Mania - Pediatrics
In a double-blind, placebo-controlled trial 12% (13/111) of RISPERDAL®-treated patients discontinued due to an adverse reaction, compared with 7% (4/58) of placebo-treated patients. The adverse reactions associated with discontinuation in more than one RISPERDAL®-treated pediatric patient were nausea (3%), somnolence (2%), sedation (2%), and vomiting (2%).
Autistic Disorder - Pediatrics
In the two 8-week, placebo-controlled trials in pediatric patients treated for irritability associated with autistic disorder (n = 156), one RISPERDAL®-treated patient discontinued due to an adverse reaction (Parkinsonism), and one placebo-treated patient discontinued due to an adverse event.
Dose Dependency of Adverse Reactions in Clinical Trials
Extrapyramidal Symptoms
Data from two fixed-dose trials in adults with schizophrenia provided evidence of dose-relatedness for extrapyramidal symptoms associated with RISPERDAL® treatment.
Two methods were used to measure extrapyramidal symptoms (EPS) in an 8-week trial comparing 4 fixed doses of RISPERDAL® (2, 6, 10, and 16 mg/day), including a Parkinsonism score (mean change from baseline) from the Extrapyramidal Symptom Rating Scale, and incidence of spontaneous complaints of EPS:
Table 16.
Dose Groups |
Placebo |
RISPERDAL® 2 mg |
RISPERDAL® 6 mg |
RISPERDAL® 10 mg |
RISPERDAL® 16 mg |
Parkinsonism |
1.2 |
0.9 |
1.8 |
2.4 |
2.6 |
EPS Incidence |
13% |
17% |
21% |
21% |
35% |
Similar methods were used to measure extrapyramidal symptoms (EPS) in an 8-week trial comparing 5 fixed doses of RISPERDAL® (1, 4, 8, 12, and 16 mg/day):
Table 17.
Dose Groups |
RISPERDAL® 1 mg |
RISPERDAL® 4 mg |
RISPERDAL® 8 mg |
RISPERDAL® 12 mg |
RISPERDAL® 16 mg |
Parkinsonism |
0.6 |
1.7 |
2.4 |
2.9 |
4.1 |
EPS Incidence |
7% |
12% |
17% |
18% |
20% |
Dystonia
Class Effect: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.
Other Adverse Reactions
Adverse event data elicited by a checklist for side effects from a large study comparing 5 fixed doses of RISPERDAL® (1, 4, 8, 12, and 16 mg/day) were explored for dose-relatedness of adverse events. A Cochran-Armitage Test for trend in these data revealed a positive trend (p<0.05) for the following adverse reactions: somnolence, vision abnormal, dizziness, palpitations, weight increase, erectile dysfunction, ejaculation disorder, sexual function abnormal, fatigue, and skin discoloration.
Changes in Body Weight
Weight gain was observed in short-term, controlled trials and longer-term uncontrolled studies in adult and pediatric patients [see Warnings and Precautions Adverse Reactions (6), and Use in Specific Populations].
Changes in ECG Parameters
Between-group comparisons for pooled placebo-controlled trials in adults revealed no statistically significant differences between risperidone and placebo in mean changes from baseline in ECG parameters, including QT, QTc, and PR intervals, and heart rate. When all RISPERDAL® doses were pooled from randomized controlled trials in several indications, there was a mean increase in heart rate of 1 beat per minute compared to no change for placebo patients. In short-term schizophrenia trials, higher doses of risperidone (8–16 mg/day) were associated with a higher mean increase in heart rate compared to placebo (4–6 beats per minute). In pooled placebo-controlled acute mania trials in adults, there were small decreases in mean heart rate, similar among all treatment groups.
In the two placebo-controlled trials in children and adolescents with autistic disorder (aged 5 – 16 years) mean changes in heart rate were an increase of 8.4 beats per minute in the RISPERDAL® groups and 6.5 beats per minute in the placebo group. There were no other notable ECG changes.
In a placebo-controlled acute mania trial in children and adolescents (aged 10 – 17 years), there were no significant changes in ECG parameters, other than the effect of RISPERDAL® to transiently increase pulse rate (< 6 beats per minute). In two controlled schizophrenia trials in adolescents (aged 13 – 17 years), there were no clinically meaningful changes in ECG parameters including corrected QT intervals between treatment groups or within treatment groups over time.
The following adverse reactions have been identified during postapproval use of risperidone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These adverse reactions include: alopecia, anaphylactic reaction, angioedema, atrial fibrillation, cardiopulmonary arrest, diabetic ketoacidosis in patients with impaired glucose metabolism, dysgeusia, hypoglycemia, hypothermia, inappropriate antidiuretic hormone secretion, intestinal obstruction, jaundice, mania, pancreatitis, pituitary adenoma, precocious puberty, pulmonary embolism, QT prolongation, sleep apnea syndrome, sudden death, thrombocytopenia, thrombotic thrombocytopenic purpura, urinary retention, and water intoxication.
|